Research in the Lab
A major question in development is how different specialized cell types arise from a common progenitor. In the adult Drosophila compound eye, color discrimination is achieved by UV-, blue-, and green-sensitive photoreceptors (PRs). These different PR subsets arise from neuronal precursors called R7 and R8 cells. Previous work of ours demonstrated that R7-based UV-sensitive PRs require the repression of R8-based blue/green-sensitive PR characteristics to properly develop (Cook et al., 2003). This repression is mediated by the transcription factor, Prospero (Pros), whose vertebrate ortholog is Prox1. More recently, we have found that Senseless (Sens), a Drosophila ortholog to the Gfi-1 transcription factor, plays an opposite role to Pros by both negatively regulating R7-based features and positively enforcing R8-based features during terminal differentiation. Moreover, we have found that Pros and Sens function together with the transcription factor Orthodenticle (Otd) to oppositely regulate R7 and R8 photoreceptor rhodopsin gene expression in vitro. These data show that sens, previously shown to be essential for neuronal specification, also controls differentiation of specific neuronal subtypes in the retina. Interestingly, Pros has recently been shown to function as a tumor suppressor, whereas Gfi-1 is a well-characterized oncogene. Thus, we propose that sens/pros antagonism is important for regulating many biological processes and are currently pursuing this line of research.
Publications
Ranade SS, Yang-Zhou D, Kong SW, McDonald EC, Cook TA, and Pignoni F. The regulation of photoperception-related genes by Otd supports the conservation of CRX/OTX/OTD gene family functions in flies and vertebrates. Dev Biol 315(2):521-34, 2008.
Xie B, Charlton-Perkins M, McDonald EC, Gebelein B, Cook TA. Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development 134:4243-4253, 2007.
Tahayato A, Sonneville R, Pichaud F, Papatsenko D, Beaufils P, Wernet M, Cook T, Desplan C. Otd/Crx, a dual regulator for the mosaic expression of Drosophila rhodopsins. Dev Cell 2003;5:391-402.
Cook T, Pichaud F, Sonneville R, Papatsenko D, and Desplan C. Distinction between color photoreceptor cell fates is controlled by Prospero in Drosophila. Dev Cell 2003;4:853-64.
Cook T. Cell diversity in the retina: More than meets the eye. Bioessays 2003;25:921-925.
Contact Information
Tiffany Cook, PhD
TCHRF 3045, MLC 7007
3333 Burnet Avenue, CCHMC
Cincinnati, OH 45229
Email: tiffany.cook@cchmc.org
Phone: 513-636-6991 (office); 513-636-1659 (lab)
